The interaction of catecholamines with alpha and beta adrenergic receptors in the CNS leads to an increase in the activity of the enzyme adenylate cyclase. It now appears that there are two subclasses of both alpha and beta adrenergic receptors in the central nervous system as well as in the periphery. Direct "in vitro" binding assays for the various subclasses of adrenergic receptor will be used to study some of the factors which regulate either the density or properties of these receptors. In addition to measuring binding sites, the effect of various physiological and pharmacological manipulations on the responsiveness of adenylate cyclase to catecholamines will be determined as will the relationship between the various subclasses of alpha-adrenergic receptor and adenylate cyclase. A fluorescent or autoradiographic assay for beta-adrenergic receptors will be established. Morphological and biochemical techniques will be used to investigate the anatomical and cellular localization of catecholamine receptors in the central nervous system. The development of catecholamine receptors and the effects of drugs on normal development will be studied in homogenates of cerebral cortex and cerebellum. The effects of pharmacological agents that affect the concentration, synthesis, metabolism, or reuptake of norepinephrine on the properties of catecholamine receptors and hormone-sensitive adenylate cyclase activity will be determined. Other experiments will investigate the role of hormones in regulating catecholamine receptors in rat liver and in cultured hepatocytes obtained from adult rats. It is hoped that the studied described in this proposal will provide new information with regard to the regulation of catecholamine receptors including their various subtypes and in terms of our understanding of the pathologic basis of and therapy useful for the treatment of neurologic and mental disease.